title: Vibrio effector protein, VopQ, forms a lysosomal gated channel that disrupts host ion homeostasis and autophagic flux.
abstract: Defects in normal autophagic pathways are implicated in numerous human diseases--such as neurodegenerative diseases, cancer, and cardiomyopathy--highlighting the importance of autophagy and its proper regulation. Herein we show that Vibrio parahaemolyticus uses the type III effector VopQ (Vibrio outer protein Q) to alter autophagic flux by manipulating the partitioning of small molecules and ions in the lysosome. This effector binds to the conserved Vo domain of the vacuolar-type H(+)-ATPase and causes deacidification of the lysosomes within minutes of entering the host cell. VopQ forms a gated channel ∼18 Å in diameter that facilitates outward flux of ions across lipid bilayers. The electrostatic interactions of this type 3 secretion system effector with target membranes dictate its preference for host vacuolar-type H(+)-ATPase-containing membranes, indicating that its pore-forming activity is specific and not promiscuous. As seen with other effectors, VopQ is exploiting a eukaryotic mechanism, in this case manipulating lysosomal homeostasis and autophagic flux through transmembrane permeation.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Anju
authors.initials: A
authors.lastname: Sreelatha
authors.forename: Terry L
authors.initials: TL
authors.lastname: Bennett
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.forename: Qiu-Xing
authors.initials: QX
authors.lastname: Jiang
authors.forename: Kim
authors.initials: K
authors.lastname: Orth
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Starai
mesh_terms: D001343:Autophagy; D001426:Bacterial Proteins / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D015640:Ion Channel Gating; D007477:Ions; D008247:Lysosomes / Q000502:physiology*; D014736:Vibrio parahaemolyticus / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D007477:Ions
keywords: microbial pathogenesis; virulence; yeast vacuole